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Computational simulations suggest multiple sclerosis is a single disease

Research at the University of Barcelona, published in PLOS Computational Biology, supports the view that multiple sclerosis, the symptoms and progression of which vary widely between patients, is nonetheless a single disease with consistent underlying mechanisms. Multiple sclerosis is an autoimmune disease that can cause a variety of problems, including blurred vision, impaired memory, and paralysis. Symptoms and patterns of disease progression over time vary among patients, leading to suggestions that it may consist of two or more different diseases. The researchers hypothesised that multiple sclerosis is a single disease with differing outcomes for different patients, but all driven by the same underlying biological mechanism: an immune system attack upon the protective sheaths around nerve cells, resulting in chronic inflammation and axonal degeneration. The researchers developed a mathematical model of multiple sclerosis based on experimental data from 66 patients who had been followed for up to 20 years. They used the model for computational simulations of the various biological processes known to be involved in the disease. To test the validity of their model, the investigators also ran simulations with data from a second group of 120 patients with multiple sclerosis. They found that changing the intensity of the underlying biological processes involved in multiple sclerosis at particular time points reproduced the variability of the disease courses seen in these patients. Their results support the hypothesis that the various symptoms and disease courses associated with multiple sclerosis are produced by the same underlying mechanisms. “This concept has significant therapeutic implications and will drive the development of new therapies because it implies that multiple sclerosis will produce significant disability if had for enough time in all patients,” says co-author Dr Pablo Villoslada. “Indeed, preventing relapses, although very important, will not be enough to achieve good control of the disease.”

http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005757

Afternoon heart surgery linked to better outcomes for patients

Outcomes for open heart surgery may be improved by moving surgery from the morning to the afternoon, according to a study published in The Lancet. The researchers identified a link between an individual’s circadian clock and their risk of heart damage and major cardiac events after heart surgery. The study also provides early insights into the mechanism behind this link, finding that the expression of nearly 300 genes in myocardial tissue varied according to the time of day. After open heart surgery, some patients develop damage to the heart that affects its ability to pump blood, resulting in poor outcomes, including heart failure and a heightened risk of death. Previous research has suggested that cardiovascular events (such as myocardial infarction) in the morning may be associated with a higher risk of damage than afternoon events, but the reasons have been unclear. The Lancet study, from the University of Lille in France, included an observational investigation of the association between time of day of surgery and outcomes, a randomised controlled trial investigating whether there was a causal link between the two, and a human tissue analysis to identify genes involved in the circadian effect on heart surgery. In the 6-year observational study, researchers tracked the medical records of 596 people who had had heart valve replacement surgery (half with surgery in the morning, half in the afternoon) for 500 days, to monitor any major cardiac events, such as a heart attack, heart failure or death from heart disease. Patients who had afternoon surgery had a 50% lower risk of a major cardiac event than those who had surgery in the morning (9.4% compared with 18.1%), which is equivalent to one major event avoided for every 11 patients who had afternoon surgery. In the randomised controlled trial, conducted from January 2016 to February 2017, 88 patients were randomly scheduled for heart valve replacement surgery in the morning or afternoon, and their health was monitored until they left hospital. There were no deaths in either group, and the average stay in hospital was 12 days. Patients who had afternoon surgery had lower levels of heart tissue damage after surgery than patients who had morning surgery. The researchers then tested 30 heart tissue samples from a subgroup of patients included in the trial (14 from the morning surgery group, 16 from the afternoon surgery group). They found that the afternoon surgery samples more quickly regained their ability to contract when placed in conditions that replicated the heart refilling with blood. Genetic analysis found that 287 genes in myocardium were differentially active in the afternoon and morning surgery samples. This suggests that cardiac physiology is subject to the activity of the body’s circadian clock, and that surgical outcomes reflect the heart’s poorer ability to repair itself in the morning than in the afternoon.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32132-3/fulltext